Ascorbate as a Bioactive Compound in Cancer Therapy: The Old Classic Strikes Back

Area of Science:

• Oncology
• Biochemistry
• Nutritional Science

Background:

• Cancer remains a leading cause of mortality, with treatments often causing severe adverse events.
• Ascorbate (vitamin C) is a water-soluble antioxidant not synthesized in humans.
• Ascorbate exhibits dose-dependent effects, acting as an antioxidant at low doses and inducing oxidative stress at high intravenous doses.

Purpose of the Study:

• To review evidence on ascorbate's role in cancer treatment.
• To explore ascorbate's potential as a novel, safe cancer therapy adjuvant.
• To investigate ascorbate's interaction with iron and its role in ferroptosis.

Main Methods:

• Literature review of existing studies on ascorbate and cancer.
• Analysis of ascorbate's biochemical mechanisms, including oxidative stress induction and ferroptosis.
• Examination of ascorbate's potential as an adjuvant in various cancer therapies.

Main Results:

• High-dose intravenous ascorbate can induce oxidative stress and cell death in cancer cells, particularly those with a high mitotic index.
• Ascorbate's interaction with iron is key to its pro-oxidant effects.
• Emerging evidence links ascorbate to ferroptosis, a form of oxidative stress-mediated cell death.

Conclusions:

• Ascorbate shows potential as an adjuvant to enhance radiotherapy, radio-chemotherapy, chemotherapy, and immunotherapy.
• Ascorbate may facilitate tumor cell death through reactive oxygen species generation and ferroptosis.
• Revisiting ascorbate could lead to novel, safe cancer treatment strategies for human medicine.